A program of investigation directed towards the isolation and purification of human renal renin from cadaver kidney cortex is described. The goals of this research: (1) the subsequent characterization of renin as a protein and as enzyme; (2) clarification of the role of renin precursor(s); and (3) development of a radioimmunoassay for the direct measurement of renin to further elucidate its role in the pathogenesis of hypertension. Based upon our previously reported success in the application of affinity chromatography to human renal renin purification, a protocol combining conventional chromatographic technique with three separate affinity chromatographic separations using the following ligands: pepstatin and the competitive octapeptide inhibitors (D-leu6) and pro3-(phe6) is described. A similar protocol will be undertaken for the isolation of presumed renin precursor and the nature of both in vivo and in vitro conversion to active renin will be investigated. Once purified, renal renin and prorenin will be subjected to tests of homogeneity and study as pure proteins and thereafter used as antigens in the development of a radioimmunoassay for the direct measurement of renin content. By comparison of renin content to the currently available plasma renin activity measured as generation of angiotensin 1, information will be derived regarding the role of renin in blood pressure homeostasis and in the pathogenesis of hypertension.